Skip to main content
SpringerLink
Log in
Book cover

Notch Signaling in Embryology and Cancer pp 199–209Cite as

Notch, Apoptosis and Cancer

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 727))

Abstract

Proper embryonic development and normal tissue homeostasis require a series of molecular processes, regulating cell growth, differentiation and apoptosis. Perturbation in any of these processes invariably contributes to the development of cancer. In particular, defects in apoptosis are seen in virtually all types of human cancers. The Notch pathway plays an important role in cell fate determination in both embryonic development and organ homeostasis. Not surprisingly, Notch also plays a role in cancer when it is dysregulated. In this chapter, we will explore how Notch signaling interacts with key pathways that regulate apoptosis in cancer. Particularly, we will focus on the relationship between Notch and proteins responsible for activation of the caspase pathway. Notch regulates apoptosis through extensive networks, involving cell cycle, growth and survival pathways. Thus, we will also examine how apoptosis is modulated by the crosstalk between Notch and other signaling pathways such as p53, NF-κB and PI3K-Akt pathways.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26:239–257.

    Article  PubMed  CAS  Google Scholar 

  2. Danial Nika N, Korsmeyer Stanley J. Cell death: critical control points. Cell 2004; 116:205–219.

    Article  PubMed  CAS  Google Scholar 

  3. Bredesen Dale E, Rao Rammohan V, Mehlen Patrick. Cell death in the nervous system. Nature 2006; 443:796–802.

    Article  PubMed  CAS  Google Scholar 

  4. Chang Mi-Kyung, Binder Christoph J, Miller Yury I et al. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med 2004; 200:1359–1370.

    Article  PubMed  CAS  Google Scholar 

  5. Cory S, Strasser A, Jacks T et al. Enhanced cell survival and tumorigenesis Cold Spring Harb Symp. Quant Biol 1994; 59:365–375.

    CAS  Google Scholar 

  6. Morgan TH. The Theory of the Gene. The American Naturalist 1917; 51:513.

    Article  Google Scholar 

  7. Wharton KA, Johansen KM, Xu T et al. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 1985; 43:567–581.

    Article  PubMed  CAS  Google Scholar 

  8. Shellenbarger DL, Mohler JD. Temperature-sensitive periods and autonomy of pleiotropic effects of l(1) Nts1, a conditional notch lethal in Drosophila. Dev Biol 1978; 62:432–446.

    Article  PubMed  CAS  Google Scholar 

  9. Roy Monideepa, Pear Warren S, Aster Jon C. The multifaceted role of Notch in cancer. Curr Opin Genet Dev 2007; 17:52–59.

    Article  Google Scholar 

  10. Curry Christine L, Reed Laura L, Golde Todd E et al. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi’s sarcoma tumor cells. Oncogene 2005; 24:6333–6344.

    PubMed  CAS  Google Scholar 

  11. Das Indranil, Craig Colleen, Funahashi Yasuhiro et al. Notch oncoproteins depend on gamma-secretase/ presenilin activity for processing and function. J Biol Chem 2004; 279:30771–30780.

    Article  Google Scholar 

  12. Duechler M, Shehata M, Schwarzmeier JD et al. Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2. Leukemia 2005; 19:260–267.

    Article  PubMed  CAS  Google Scholar 

  13. Haruki Nobuhiro, Kawaguchi Keiko S, Eichenberger Shannon et al. Dominant-negative Notch3 receptor inhibits mitogen-activated protein kinase pathway and the growth of human lung cancers. Cancer Res 2005; 65:3555–3561.

    Article  Google Scholar 

  14. Konishi Jun, Kawaguchi Keiko S, Vo Huan et al. Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res 2007; 67:8051–8057.

    Article  Google Scholar 

  15. Osipo C, Patel P, Rizzo P et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene 2008; 27:5019–5032.

    Article  PubMed  CAS  Google Scholar 

  16. Pannequin Julie, Bonnans Caroline, Delaunay Nathalie et al. The wnt target jagged-1 mediates the activation of notch signaling by progastrin in human colorectal cancer cells. Cancer Res 2009; 69:6065–6073.

    Google Scholar 

  17. Vousden Karen H, Lane David P. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8:275–283.

    Article  PubMed  CAS  Google Scholar 

  18. Hollstein M, Sidransky D, Vogelstein B et al. p53 mutations in human cancers. Science 1991; 253:49–53.

    Article  PubMed  CAS  Google Scholar 

  19. Sanchez-Cespedes M, Reed AL, Buta M et al. Inactivation of the INK4A/ARF locus frequently coexists with TP53 mutations in nonsmall cell lung cancer. Oncogene 1999; 18:5843–5849.

    Article  PubMed  CAS  Google Scholar 

  20. Higashiyama M, Doi O, Kodama K et al. MDM2 gene amplification and expression in nonsmall-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br J Cancer 1997; 75:1302–1308.

    Article  PubMed  CAS  Google Scholar 

  21. Ladanyi M, Cha C, Lewis R et al. MDM2 gene amplification in metastatic osteosarcoma. Cancer Res 1993; 53:16–18.

    PubMed  CAS  Google Scholar 

  22. Beverly Levi J, Felsher Dean W, Capobianco Anthony J. Suppression of p53 by Notch in lymphomagenesis: implications for initiation and regression. Cancer Res 2005; 65:7159–7168.

    Article  PubMed  CAS  Google Scholar 

  23. Kim SB, Chae GW, Lee J et al. Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation Cell Death Differ. 2007; 14:982–991.

    PubMed  Google Scholar 

  24. Boggs Kristy, Henderson Brystol, Reisman David. RBP-Jkappa binds to and represses transcription of the p53 tumor suppressor gene. Cell Biol Int 2009; 33:318–324.

    Article  Google Scholar 

  25. Gulino Alberto, Di Marcotullio Lucia, Screpanti Isabella. The multiple functions of Numb Exp. Cell Res 2010; 316:900–906.

    Article  Google Scholar 

  26. Westhoff Britta, Colaluca Ivan N, D’Ario Giovanni et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA 2009; 106:22293–22298.

    Article  Google Scholar 

  27. Pece Salvatore, Serresi Michela, Santolini Elisa et al. Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. J Cell Biol 2004; 167:215–221.

    Article  Google Scholar 

  28. Colaluca Ivan N, Tosoni Daniela, Nuciforo Paolo et al. NUMB controls p53 tumour suppressor activity. Nature 2008; 451:76–80.

    Article  PubMed  CAS  Google Scholar 

  29. Wang Chunmei, Qi Runzi, Li Nan et al. Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. J Biol Chem 2009; 284:16183–16190.

    Article  Google Scholar 

  30. Yang Xudong, Klein Rüdiger, Tian Xiaolin et al. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol 2004; 269:81–94.

    Article  Google Scholar 

  31. Lefort Karine, Mandinova Anna, Ostano Paola et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCKalpha kinases. Genes Dev 2007; 21:562–577.

    Article  Google Scholar 

  32. Alimirah Fatouma, Panchanathan Ravichandran, Davis Francesca J et al. Restoration of p53 expression in human cancer cell lines upregulates the expression of Notch1: implications for cancer cell fate determination after genotoxic stress. Neoplasia 2007; 9:427–434.

    Article  Google Scholar 

  33. Wei Chia-Lin, Wu Qiang, Vega Vinsensius B et al. A global map of p53 transcription-factor binding sites in the human genome. Cell 2006; 124:207–219.

    Article  Google Scholar 

  34. Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 2006; 25:6817–6830.

    Article  PubMed  Google Scholar 

  35. White DW, Roy A, Gilmore TD. The v-Rel oncoprotein blocks apoptosis and proteolysis of I kappa B-alpha in transformed chicken spleen cells. Oncogene 1995; 10:857–868.

    PubMed  CAS  Google Scholar 

  36. Beg AA, Sha WC, Bronson RT et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature 1995; 376:167–170.

    Article  PubMed  CAS  Google Scholar 

  37. Oswald F, Liptay S, Adler G et al. NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa. Mol Cell Biol 1998; 18:2077–2088.

    PubMed  CAS  Google Scholar 

  38. Cheng P, Zlobin A, Volgina V et al. Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. J Immunol 2001; 167:4458–4467.

    PubMed  CAS  Google Scholar 

  39. Oakley Fiona, Mann Jelena, Ruddell Richard G et al. Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator. Notch1 J Biol Chem 2003; 278:24359–24370.

    Google Scholar 

  40. Bash J, Zong WX, Banga S et al. Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. EMBO J 1999; 18:2803–2811.

    Article  PubMed  CAS  Google Scholar 

  41. Moran Stewart T, Cariappa Annaiah, Liu Haoyuan et al. Synergism between NF-kappa B1/p50 and Notch2 during the development of marginal zone B lymphocytes. J Immunol 2007; 179:195–200.

    PubMed  CAS  Google Scholar 

  42. Guan E, Wang J, Laborda J et al. T-cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T-cells. J Exp Med 1996; 183:2025–2032.

    Article  PubMed  CAS  Google Scholar 

  43. Wang J, Shelly L, Miele L et al. Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain. J Immunol 2001; 167:289–295.

    PubMed  CAS  Google Scholar 

  44. Shin Hyun Mu, Minter Lisa M, Cho Ok Hyun et al. Notch1 augments NF-kappaB activity by facilitating its nuclear retention. EMBO J 2006; 25:129–138.

    Article  Google Scholar 

  45. Vilimas Tomas, Mascarenhas Joaquina, Palomero Teresa et al. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med 2007; 13:70–77.

    Article  Google Scholar 

  46. Fernández-Majada V, Aguilera C, Villanueva A et al. Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci USA 2007; 104:276–281.

    Article  PubMed  Google Scholar 

  47. Paez Juan, Sellers William R. PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res 2003; 115:145–167.

    Google Scholar 

  48. Keniry M, Parsons R. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008; 27:5477–5485.

    Article  PubMed  CAS  Google Scholar 

  49. Rangarajan A, Syal R, Selvarajah S et al. Activated Notch1 signaling cooperates with papillomavirus oncogenes in transformation and generates resistance to apoptosis on matrix withdrawal through PKB/Akt. Virology 2001; 286:23–30.

    Article  PubMed  CAS  Google Scholar 

  50. Konishi J, Yi F, Chen X et al. Notch3 cooperates with the EGFR pathway to modulate apoptosis through the induction of bim. Oncogene 2010; 29:589–596.

    Article  PubMed  CAS  Google Scholar 

  51. Stylianou Spyros, Clarke Rob B, Brennan Keith. Aberrant activation of notch signaling in human breast cancer. Cancer Res 2006; 66:1517–1525.

    Article  Google Scholar 

  52. Meurette Olivier, Stylianou Spyros, Rock Rebecca et al. Notch activation induces Akt signaling via an autocrine loop to prevent apoptosis in breast epithelial cells. Cancer Res 2009; 69:5015–5022.

    Google Scholar 

  53. Bedogni Barbara, Warneke James A, Nickoloff Brian J et al. Notch1 is an effector of Akt and hypoxia in melanoma development. J Clin Invest 2008; 118:3660–3670.

    Article  Google Scholar 

  54. Palomero Teresa, Sulis Maria Luisa, Cortina Maria et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med 2007; 13:1203–1210.

    Article  Google Scholar 

  55. Perumalsamy Lakshmi R, Nagala Manjula, Sarin Apurva. Notch-activated signaling cascade interacts with mitochondrial remodeling proteins to regulate cell survival. Proc Natl Acad Sci USA 2010; 107:6882–6887.

    Article  PubMed  CAS  Google Scholar 

  56. Eliasz S, Liang S, Chen Y et al. Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway. Oncogene 2010; 29:2488–2498.

    Article  PubMed  CAS  Google Scholar 

  57. Williams O, Norton T, Halligey M et al. The action of Bax and bcl-2 on T-cell selection. J Exp Med 1998; 188:1125–1133.

    Article  PubMed  CAS  Google Scholar 

  58. Hamnér S, Skoglösa Y, Lindholm D. Differential expression of bcl-w and bcl-x messenger RNA in the developing and adult rat nervous system. Neuroscience 1999; 91:673–684.

    Article  PubMed  Google Scholar 

  59. Bouillet Philippe, Strasser Andreas. BH3-only proteins—evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002; 115:1567–1574.

    Google Scholar 

  60. Morrow David, Sweeney Catherine, Birney Yvonne A et al. Cyclic strain inhibits Notch receptor signaling in vascular smooth muscle cells in vitro. Circ Res 2005; 96:567–575.

    Article  Google Scholar 

  61. Wang Zhiwei, Zhang Yuxiang, Li Yiwei et al. Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther 2006; 5:483–493.

    Google Scholar 

  62. Sade Hadassah, Krishna Sudhir, Sarin Apurva. The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T-cells. J Biol Chem 2004; 279:2937–2944.

    Google Scholar 

  63. Nefedova Yulia, Sullivan Daniel M, Bolick Sophia C et al. Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood 2008; 111:2220–2229.

    Article  Google Scholar 

  64. Qin Jian-Zhong, Stennett Lawrence, Bacon Patricia et al p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas. Mol Cancer Ther 2004; 3:895–902.

    Google Scholar 

  65. Wilson Nicholas S, Dixit Vishva, Ashkenazi Avi. Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 2009; 10:348–355.

    Article  PubMed  CAS  Google Scholar 

  66. Quillard Thibaut, Devalliere Julie, Chatelais Mathias et al. Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin. PLoS One 2009; 4:e8244.

    Article  Google Scholar 

  67. Bushell Martin, Stoneley Mark, Kong Yi Wen et al. Polypyrimidine tract binding protein regulates IRES-mediated gene expression during apoptosis. Mol Cell 2006; 23:401–412.

    Article  Google Scholar 

  68. Wang Wenli, Prince Chengyu Z, Mou Yongshan et al. Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis. J Biol Chem 2002; 277:21723–21729.

    Article  Google Scholar 

  69. Bheeshmachar Geetha, Purushotaman Divya, Sade Hadassah et al. Evidence for a role for notch signaling in the cytokine-dependent survival of activated T-cells. J Immunol 2006; 177:5041–5050.

    Google Scholar 

  70. O’Riordan Mary XD, Bauler Laura D, Scott Fiona L et al. Inhibitor of apoptosis proteins in eukaryotic evolution and development: a model of thematic conservation. Dev Cell 2008; 15:497–508.

    Article  PubMed  Google Scholar 

  71. Rosati Emanuela, Sabatini Rita, Rampino Giuliana et al. Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood 2009; 113:856–865.

    Article  Google Scholar 

  72. Liu Wen-Hsien, Hsiao Huey-Wen, Tsou Wen-I et al. Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation. EMBO J 2007; 26:1660–1669.

    Article  Google Scholar 

  73. Jemal Ahmedin, Siegel Rebecca, Ward Elizabeth et al. Cancer statistics, 2009 CA. Cancer J Clin 2009; 59:225–249.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA

    Thao P. Dang

Authors
  1. Thao P. Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Dermatology, The Saarland University Hospital, Homburg, Germany

    Jörg Reichrath

  2. Department of Internal Medicine I, The Saarland University Hospital, Homburg, Germany

    Sandra Reichrath

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Dang, T.P. (2012). Notch, Apoptosis and Cancer. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 727. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0899-4_15

Download citation

Publish with us

Policies and ethics

Search

Navigation